title: Relationship between systemic cytokines and complement factor H Y402H polymorphism in patients with dry age-related macular degeneration.
abstract: OBJECTIVE
  To investigate the relationship between systemic cytokines, the complement factor H (CFH) Y402H polymorphism, drusen load, and subfoveal choroidal thickness in patients with dry age-related macular degeneration (AMD).
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Forty-four dry AMD patients under care of the Retina Service at the University of British Columbia were enrolled. Drusen load was measured with an automated software algorithm in spectral-domain optical coherence tomography; subfoveal choroidal thickness was measured manually using enhanced depth imaging. Bio-Plex suspension assays (Bio-Rad Laboratories) were used to analyze cytokines in plasma and CFH Y402H was genotyped. Statistical analyses included analysis of covariance and Pearson correlation, corrected for multiple comparisons.
  
  
  RESULTS
  The levels of 3 of 4 studied cytokines were significantly different among patients with CC, CT, or TT variants of the CFH Y402H polymorphism (P < .01). Patients with the at-risk CC variant had higher systemic levels of interleukin-6, interleukin-18, and tumor necrosis factor α than those with the CT variants, the TT variant, or both (P < .01). Interleukin-1β did not reach significance (P = .02), but did demonstrate a consistent trend. No correlation was found between plasma cytokines and drusen load or choroidal thickness (all P > .15).
  
  
  CONCLUSIONS
  The elevated systemic levels of selected proinflammatory cytokines, including those representing products of inflammasome activation, were associated with the CC at-risk variant of the Y402H polymorphism and suggest that genetic factors regulate the inflammatory status in dry AMD patients. Our data support the central role of inflammation in the pathogenesis of AMD and provide further evidence of a systemic involvement in AMD etiology.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Eye Care Centre, University of British Columbia, Vancouver, Canada.
authors.forename: Sijia
authors.initials: S
authors.lastname: Cao
authors.forename: Ashley
authors.initials: A
authors.lastname: Ko
authors.forename: Marita
authors.initials: M
authors.lastname: Partanen
authors.forename: Kaivon
authors.initials: K
authors.lastname: Pakzad-Vaezi
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Merkur
authors.forename: David A
authors.initials: DA
authors.lastname: Albiani
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Kirker
authors.forename: Aikun
authors.initials: A
authors.lastname: Wang
authors.forename: Jing Z
authors.initials: JZ
authors.lastname: Cui
authors.forename: Farzin
authors.initials: F
authors.lastname: Forooghian
authors.forename: Joanne A
authors.initials: JA
authors.lastname: Matsubara
mesh_terms: D000368:Aged; D002829:Choroid / Q000473:pathology; D017242:Complement Factor H / Q000235:genetics*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood*; D003941:Diagnostic Techniques, Ophthalmological; D060005:Genotyping Techniques; D057092:Geographic Atrophy / Q000097:blood* / Q000235:genetics*; D006801:Humans; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015593:Retinal Drusen / Q000175:diagnosis; D041623:Tomography, Optical Coherence
chemical_list: D016207:Cytokines; D017242:Complement Factor H